Obesity has reached epidemic levels in the United States. The rate of recidivism for long-term weight loss is substantial and presents a critical problem given the importance of obesity as a modifiable risk factor for diseases like type 2 diabetes. This K01 Mentored Research Scientist Award will support the candidate in establishing an independent research career using longitudinal psychobehavioral testing and neuroimaging to investigate the role of central opioid system response in obesity. The training component of this application builds on the candidate's exercise science and behavioral neuroscience background while providing a unique perspective to study the pathophysiology of obesity. The research component will examine psychobehavioral (impulse control and mood) and metabolic profiles of lean individuals and obese before and after weight loss. Probing the metabolic, psychobehavioral and neurochemical response in lean and obese individuals before and after weight loss will provide information allowing: 1) assessment of the central m-opioid systems in response to acute fasting and feeding using Positron Emission Tomography (PET) imaging; 2) identification of relationships between measures of mood and metabolism related to successful maintenance of weight loss; and 3) exploration of the relationship between metabolic function and psychobehavioral performance. The research component of this application will allow the candidate to address the following specific training aims: Aim 1: Develop skill-sets for neuropsychiatric and behavioral assessments and measurements of metabolic parameters in healthy and diseased populations. Aim 2: Conduct neuroimaging research using PET. We hypothesize that a) obese individuals will present impaired decision making, b) both mood and decision making will improve in obese individuals following weight-loss, c) overeating in obese individuals is associated with a dysregulation of MOR system function, and d) fasting MOR BPND and opioid release response from a standard meal will increase in obese individuals following weight loss. This project has high potential significance to help characterize the metabolic and psychobehavioral responses to obesity believed to share a common mechanism through central m-opioid systems, and provide novel insight into the neurohormonal and behavioral correlates of obesity and maintenance of weight loss. This mechanistic knowledge may help in the development of targeted interventions for high risk populations as well as potential treatment strategies for obesity. The project will train a promising scientist and help clarify phenotypic aspects of the pathophysiology of obesity, a significant public health priority. The proposed K01 award is well aligned with the missions of NIH and NIDDK, and Dr. Burghardt's background and career goals are in line with the commitment of NIH to translational science. The project will train a promising scientist and help clarify phenotypic aspects of the pathopyshiology of obesity, a significant public health priority. PUBLIC HEALTH RELEVANCE: The proposed K01 project serves dual purposes: (1) To train a promising scientist to become an independent translational investigator using PET neuroimaging and psychobehavioral measurements related to the pathophysiology of obesity. (2) To help understand the neural, psychobehavioral and metabolic pathophysiology of obesity; how these attributes are altered during weight loss; and provide insight into the long-term maintenance of weight loss. Accomplishment of these two objectives will address the need for translational research scientists while simultaneously answering critical questions about the neurobiological pathways of obesity and recidivism of weight loss, a significant public health priority.